Summary of Work: We examined the influence of vitamin D receptor (VDR) polymorphisms on bone mineral density (BMD), rate of change in BMD, and markers of bone metabolism in a longitudinal study during the perimenopausal years. The study included 103 women ages 40 to 54 years at baseline, followed from 1987 to 1995. BMDs at the hip, radius, and spine were measured at approximately 2 year intervals. Fasting blood and first void urine samples were obtained at the last BMD assessment and were used to determine VDR genotype and levels of 1,25(OH)2D, 25(OH)D , osteocalcin, bone-specific alkaline phosphatase (alkphos), and type I collagen products: N-telopeptide cross-linking domain (NTx) and free deoxypyridnoline (Dpyr). The mean age was 46.4 years at baseline. The rate of decline in BMD was significantly steeper among post-menopausal women at the spine (mean difference, post- vs pre-menopause, -2.1%/year), hip (-1.6%/year), and mid-radius (-1.5%/year) (p< 0.01), and there was a trend toward higher levels of the markers of bone formation and resorption. Controlling for age and menopausal status,spinal BMD at baseline was 4.6% lower in the tt genotype compared to the TT genotype (p=0.27); the difference at the distal radius was - 1.4% (p=0.79), at the mid radius, - 3.2% (p=0.16), and at the hip, + 1.7% (p=0.16). The differences between genotype in rate of decline were not statistically significant, but the steepest rate of decline was seen in the TT genotype at the spine, mid radius, and hip. There were no consistent differences by genotype in vitamin D metabolites or bone metabolism markers. Our results are consistent with a small effect (3-4%) of VDR genotype on pre- menopausal spine and mid-radius BMD, but with our sample size, these effects were not statistically significant.